Rebooting clinical researchPeter Mansell looks at the impediments to rebooting clinical research in the UK and suggests traditional approaches to the patient funnel are missing a trick
A crucial factor in the UK’s continuing viability as a competitive location for pharmaceutical R&D is its capacity not just to get clinical trials planned, approved and set up more efficiently, but to fill those trials with willing and appropriate patients.
Last year data from Quintiles showed the number of patients enrolled into mid- to late-stage trials in the UK reached 782 in 2009, not far ahead of the 749 recorded in 1999. Over the same 10-year period, recruitment numbers almost doubled to 1,283 in France, trebled to 31,617 in the US and quadrupled to 2,117 in the Czech Republic.
The global context is harder to ignore when opportunities for easier and faster recruitment are so readily available in emerging markets such as India and Central and Eastern Europe. A recent report by the Academy of Medical Sciences noted that the UK’s share of global patient recruitment fell from 6% to 2-3% between 2000 and 2006.
The National Institute for Health Research Clinical Research Network has a more encouraging story to tell. Patient recruitment into its own portfolio studies grew by nearly 70% year on year to more than 500,000 in 2010. Chief executive Dr Jonathan Sheffield acknowledges that the threat of swine flu helped to push the numbers up. All the same, he says, last year’s pandemic vaccine trials showed “how well the NHS responds in an emergency. We managed to get all our processes to be very quick and very slick”.
Nor does Sheffield buy the UK’s declining share of global recruitment as evidence of creeping obsolescence. “We’re confusing percentages with recruitment,” he comments. With huge populations in countries such as China, inevitably an increasing proportion of trials will be carried out in those markets. “If you look at the number of people going into trials, ours are going up,” Sheffield adds. “The volume, the proportionality across the world, is different because the economic profile is changing.”
One testament to the effectiveness of the NIHR networks is the flow of patients into cancer studies. Last November the National Cancer Research Network reported that the number of cancer patients enrolling in UK clinical trials over the past decade had risen from one in every 26 patients diagnosed to around one in six. That patient recruitment remains a source of concern in the sector, though, is evident from a recent survey run by the Medical Research Network, a UK-based clinical trial support organisation that uses research nurses to help keep trials on track either at sites or in patients’ own homes.
Survey participants, who work across a broad range of clinical research functions, were asked to list what they felt were the three most important issues/challenges in clinical trials today. Among the 212 responses received, recruitment was identified as by far the most significant issue, with 55 mentions versus 28 for the next most important challenge (cost).
Bureaucratic set up
Dr Graham Wylie, chief executive officer of the MRN, sees patient recruitment difficulties in the UK as partly a legacy of lengthy and complex set-up procedures for clinical trials. “We went over the years from a relatively simple set-up process to one of the most bureaucratic in the world,” he comments.
The AMS report highlights delays and uncertainties in obtaining NHS permissions as “the major bottleneck” in health research, with a particular impact on ability to recruit patients and initiate trials. Respondents to the AMS review blamed these obstacles for shortening the window of opportunity for recruitment and for pharmaceutical companies either reducing their recruitment targets in the UK or leaving the country out of multinational trials altogether.
“We have to get slicker and slicker at the way we set things up,” Sheffield agrees. There is no doubt “that if your processes are high quality and speedy, everybody is much more actively engaged. So that’s about active process management as opposed to outcomes management”.
Wylie also cites resourcing challenges in the NHS, where capacity to take on extra work has been “pared right down”. Another disadvantage is that the UK population is “culturally more likely to demand an individual service” than patients in emerging countries. In this context, Wylie argues, offering a service such as home trial support, which the MRN credits with boosting recruitment in the studies it has managed by at least 50%, is more likely to drive significant changes in uptake. “You can’t play down the infrastructure issues,” he comments. “And they do mean that hospitals are not a great place to run non-core (to the NHS) clinical trial work. It is easy to see why patients would prefer to be seen in the home.”
Another oft-cited impediment to rebooting clinical research in the UK is cultural resistance within the NHS. For Sheffield, the country should really be playing to its strengths. “We invented the randomised controlled clinical trial. We are experts in the methodology and the techniques, and therefore we should still have a very high proportion of our patients involved in research.”
NHS is “anti-commercial”
Wylie is sceptical. In a system of ‘socialised’ medicine there is a “lack of understanding of return on investment” among patients and especially staff, he asserts. The NHS regards itself as a service to the community and “is still anti-commercial”.
Only around 6% of doctors in the UK will actually get involved in trials, Wylie says. Yet MRN surveys indicate that 25% of doctors would like to participate. This is why, Wylie believes, recruiters need to focus on pragmatic issues that deter patient involvement, such as travel, car-parking charges or just a plain dislike of hospitals. Around half of all patients offered clinical trials turn them down, he notes.
For Sheffield, though, part of the challenge is “engaging patients before they become patients”. The real achievement of the NIHR CRN’s NHS engagement programme will be “when I’ve got patients coming in saying, what research can I be involved in with this condition?”
According to the AMS report, some doctors may actually be discouraging patients from enrolling in trials because they do not understand the process and/or are over-paternalistic towards patients. Moreover, statistics from the MRN’s physician interactions indicate that, of the 6% who do take part in trials, one third never do so again.
Sheffield believes that when doctors grasp the significance of research to the NHS, they are ready to champion recruitment. “My personal experience of when I’ve introduced a trials culture into an organisation [Yeovil District Hospital] that didn’t previously have a trials culture was that, once the doctors and nurses got it, their enthusiasm was boundless.”
Nor does the principle of free healthcare have to hold patients back, he argues. “The public believes that wherever they get NHS care, they’re getting the best… What we need to say is that the very best actually has to be delivered in an environment that embraces research.”
A second objective of the MRN’s survey was to look at the tools and techniques being used to achieve patient recruitment/retention and how cost-effective respondents perceive them to be. What emerged was that the most effective tools – those with high scores for frequency of use, cost-effectiveness and absolute effectiveness – are still what Wylie terms the “classic” approaches: in-house investigator databases, site training and site resources. Respondents were much less convinced by strategies such as call centres, direct-to-patient websites, third-party patient databases or research networks.
According to Wylie, this kind of conservatism is not consistent with anecdotal evidence Even the more senior people involved in clinical research tell the MRN that new media such as television and the web are “gaining ground”. While medical information has always been a leading focus of internet usage, “I don’t think patients are particularly comfortable putting their personal medical data onto websites, nor are hospital sites comfortable with adding lots of their patient demographics”, Wylie comments. And pharmaceutical companies are wary of the new media, regarding them as “too broad-brush”.
The MRN also reviewed its survey results in the light of research published last year by Cutting Edge Information. This found that six of the 17 recruitment tools evaluated by Cutting Edge had no focus on any of the patient motivators identified in the survey, such as increased access to therapy/medical care or convenience of trial sites. The take-out message, the MRN concludes, is that recruitment and retention tools tend to centre on pushing up the volume of patients going into trials, a strategy that is both expensive and increasingly outmoded. Instead, recruiters should be trying to widen the recruitment ‘funnel’ (the process by which patients are screened, referred and otherwise filtered for trial participation) at all levels – not just trying to feed more patients into the top, but assessing factors such as patient motivators or site resources that open up bottlenecks at the bottom.
The patient funnel
Traditional approaches to the patient funnel are about increasing access to a broader patient population more rapidly, Wylie observes. The assumption is that if only 2% of patients will agree to participate in a trial, then doubling the number entering the funnel will double the number coming out at the other end. “What we’re saying is that those tools are all very powerful but they’re missing a trick, and the trick is further down the funnel… It’s those patient motivators down at the bottom end that we haven’t done a lot of work on as a sector, although a number of the clinical trial support organisations have made them their focus.”
Most patient concerns around clinical trials have to do with convenience, cost and access to medicines, Wylie says. “We can’t affect whether they get access to the drugs or not but we can help by reducing the cost and impact of the trial on their lives.”
So there is potential not just to double the available patient population, by putting more patients into the top of the funnel, but to double the number of patients within that population who will actually consent to entering a trial after passing through all of the recruitment filters.
One of the reasons trials lose patients, Wylie adds, is because pharmaceutical companies and contract research organisations “aren’t allowed to get too close” to them. This “has to come from the sites, and the sites aren’t always sufficiently interested”. Site management organisations understand what the companies are trying to achieve and can “get someone to go into the hospital site, find the patient, push the patient through, and mould the site’s driving forces so they are more likely to motivate the patient and meet the sponsor’s need for speed”.
Sheffield would like to see this kind of mentality taken up by the NIHR networks. “We need to performance-manage the recruitment at a micro level, so that we’re not surprised when we’re drifting off target,” he says. “At the moment I still don’t believe we do that systematically.”
Micro-management pays off
Initiatives such as the North West Exemplar Programme (NWEP), though, have shown micro-management can pay off. Here, Sheffield points out, recruitment is being process-managed on a weekly basis to ensure targets are met – something commercial organisations such as Synexus (an SMO) do as a matter of course.
As for recruitment tools, everyone sets great store by social media but “these media hit an age group that isn’t necessarily the population for the disease”, Sheffield comments. They may be a “fantastic” way to reach children or adolescents but the average retiree “doesn’t use social media”.
What seems to “generate better numbers” is a systematic rather than opportunistic approach, Sheffield suggests. “The success we had in Yeovil in the 1990s was a simple question of reviewing the notes before the patient came to the clinic and identifying which trial they could be recruited into, then leaving that prompt on the notes for both the doctor and the patient.” In future, access to patient data – handled appropriately – will be “incredibly important” in driving recruitment, Sheffield acknowledges. But until issues such as patient confidentiality are clarified, “it does rely very much on the patient-clinician relationship”.